Will the FDA approve any psychedelic substance for medical use before 2027?

COMP360 demonstrates a significantly benign cardiac safety profile. COMPASS Pathways' COMP360 (synthetic psilocybin) Phase III safety data for treatment-resistant depression reveals a notably more benign profile regarding cardiac safety compared to concerns raised during the 2024 FDA MDMA advisory. The trials reported no instances of QTc prolongation exceeding 30 milliseconds from baseline, which is a critical indicator of cardiac safety. Furthermore, overall cardiac-related adverse events occurred at a rate of less than 1%, a finding that stands in stark contrast to the notable sympathomimetic effects observed with MDMA.

COMP360 also shows reassuring liver and hemodynamic outcomes. Regarding liver function, COMP360's data provides high reassurance, with 87% of patients experiencing only transient elevations in liver enzymes (ALT/AST) less than three times the upper limit of normal (<3xULN) and no cases meeting Hy's Law criteria. This favorable outcome contrasts sharply with the FDA's benchmark of 7% severe liver toxicity highlighted during the MDMA review. Hemodynamic effects of COMP360 were also mild and transient, with less than 10% of participants experiencing a systolic blood pressure increase of >=20 mmHg, which represents a substantial improvement over MDMA's profile where 46% of participants saw such increases.

The COMP360 safety data addresses key regulatory concerns. This robust and thoroughly monitored safety profile for COMP360 directly addresses the specific cardiac and hepatic safety concerns that challenged MDMA's regulatory path. The proactive trial design, including comprehensive ECG and vital sign monitoring, positions COMP360 with a strong risk-benefit profile for potential regulatory approval. This data significantly de-risks COMPASS Pathways' New Drug Application, potentially paving a smoother path for the first psychedelic approval before 2027.

The FDA's Psychopharmacologic Drugs Advisory Committee (PDAC) faces significant uncertainty in its composition for future reviews. As of early 2026, the committee is severely underpopulated, with only 3 voting members against a charter for 11, leaving 8 vacancies to be filled. This presents a critical factor for any potential late 2026 psychedelic drug review, especially since only one current member's term extends into that timeframe and no specific psychedelic research expertise is listed. Future appointments are likely to prioritize experts in clinical trial methodology, psychedelic research, biostatistics, and psychotherapy, directly responding to past review challenges.

The FDA and PDAC have established a clear institutional stance against functional unblinding. This position serves as a doctrinal basis for future reviews. The June 2024 meeting on MDMA-assisted therapy revealed profound skepticism from committee members towards data compromised by unblinding, questioning the reliability of efficacy signals due to potential expectation and performance bias. This stance is further cemented by the FDA's June 2023 draft guidance, which explicitly addresses the unblinding problem and recommends mitigation strategies such as blinding questionnaires.

The sole precedent for a psychedelic drug approval vote resulted in overwhelmingly negative outcomes. The June 4, 2024, review of MDMA for PTSD saw votes of 9-2 against efficacy and 10-1 that risks outweighed benefits. This outcome was a direct consequence of perceived flaws in study design and compromised data integrity due to functional unblinding, rather than a rejection of the drug's therapeutic potential itself. This precedent establishes a very high methodological bar, emphasizing that future sponsors must present exceptionally robust and unbiased trial data to secure FDA approval for psychedelic substances.

Definium Therapeutics cannot submit a complete New Drug Application (NDA) for DT120 and secure FDA approval before January 1, 2027, if subject to a standard 10-month review cycle. To meet such an approval deadline, the NDA would have required submission by approximately December 30, 2025, which precedes the readout of any of the company's three pivotal Phase 3 trials scheduled for 2026.

A Priority Review pathway offers a potential, but challenging, pre-2027 approval. A potential pathway to pre-2027 approval exists via a 6-month Priority Review, for which DT120 is a strong candidate due to its existing FDA Breakthrough Therapy Designation for Generalized Anxiety Disorder (GAD). Under this expedited timeline, the latest possible NDA submission date is approximately May 1, 2026. This aggressive schedule would necessitate the exclusion of data from the confirmatory Panorama trial, which is expected in H2 2026, and relies on an exceptionally rapid transition from the Q2 2026 topline data release of the Voyage trial to a comprehensive NDA submission.

Expedited timelines face substantial risks due to data compilation challenges. The gap between topline data release and a full, NDA-ready submission presents a critical challenge, typically requiring 3-6 months for completion. Even with the Voyage trial data anticipated in early Q2 2026, a May 1, 2026, submission date is exceptionally tight. The possibility of a Rolling Review, often permitted with Breakthrough Therapy Designation, could mitigate some of this lag by allowing sections of the NDA to be submitted as completed, but significant timeline risks remain.

COMP360 and DLX-001 demonstrate strong CMC readiness and low regulatory risk. An analysis of publicly available information up to early 2026 reveals a de-risked and mature Chemistry, Manufacturing, and Controls (CMC) program for Compass Pathways' COMP360, contradicting initial concerns about significant manufacturing or regulatory issues. Corporate leadership has explicitly stated that CMC data packages are "well in hand", with the final 26-week clinical data readout from the COMP006 study, rather than CMC readiness, identified as the primary gating item for NDA submission. Similarly, Delix Therapeutics' lead candidates, such as DLX-001, are described as "easily manufactured small molecules", and the company successfully received FDA clearance for its Investigational New Drug (IND) application for a Phase II trial, inherently requiring an adequate CMC data package for its stage of development.

COMP360's manufacturing process and FDA engagement de-risk its CMC. For COMP360, Compass Pathways utilizes a proprietary, scalable synthetic manufacturing process to produce a high-purity, crystalline GMP grade active pharmaceutical ingredient, which mitigates concerns about raw material inconsistencies or variability. The company's recent positive Type B FDA meeting and subsequent agreement on a rolling review process for the NDA are expected to accelerate the commercial launch timeline by 9-12 months. This accelerated timeline strongly suggests regulatory alignment and confidence from both parties in the development program, including the CMC aspects, thereby contradicting the notion of unresolved, delay-inducing CMC issues.

Delix's DLX-001 shows low manufacturing complexity with regulatory approval. Delix Therapeutics' novel psychoplastogen compounds, including DLX-001, are highlighted by the company as "easily manufactured small molecules," inherently reducing the manufacturing complexity and risk often associated with novel drug development. The FDA's clearance of Delix's IND for a Phase II trial design for DLX-001 is critical evidence, confirming that the CMC information provided to the agency was deemed adequate to support human trials. There is no publicly available information detailing manufacturing scale-up challenges, stability issues, or specific FDA concerns that would indicate a heightened risk of a future Complete Response Letter (CRL) independent of clinical data, beyond general industry-wide supply chain challenges.

COMP360 is projected for 6-month Priority Review due to key criteria. Compass Pathways' COMP360, a psilocybin-based therapy for Treatment-Resistant Depression (TRD), is expected to receive a 6-month Priority Review from the FDA for its New Drug Application (NDA). This accelerated timeline, a primary goal under the PDUFA framework, is anticipated because Treatment-Resistant Depression is recognized as a "serious condition". Additionally, COMP360 has shown preliminary evidence of offering a "significant improvement" over existing therapies, meeting key criteria for Priority Review designation.

Breakthrough Therapy designation strengthens the case for accelerated review. The Breakthrough Therapy designation previously granted to COMP360 significantly enhances its eligibility for Priority Review. This designation signals the FDA's early recognition of the drug's potential for substantial improvement and ensures intensive agency guidance throughout its development. This collaborative process inherently streamlines the submission, making a 6-month review feasible and appropriate for therapies like COMP360.

The market for psychedelic substance approval is influenced by several positive developments. Compass Pathways is a key player, with 26-week results from its Phase III COMP005 trial and full data from Part A of both COMP005 and COMP006 trials expected in Q1 2026. Successful outcomes from these trials are anticipated to lead to a New Drug Application (NDA) filing for COMP360 (psilocybin for Treatment-Resistant Depression) by Q3 2026, with potential FDA approval by 2027. MindMed also expects Phase 3 data for its LSD program in late 2026, and Definium's LSD-based anxiety candidate, DT120, is similarly projected for approval by 2027. The FDA has shown a willingness to streamline review processes, including accepting rolling submissions for Compass Pathways' NDA and issuing the first draft guidance for psychedelic drug development in June 2023, providing a clearer regulatory path. Conversely, the FDA's rejection of Lykos Therapeutics' MDMA-assisted therapy for PTSD in August 2024 has set a precedent of heightened regulatory scrutiny. This decision, following a negative advisory committee vote, raised concerns about trial design, functional unblinding, data integrity, cardiovascular risks, and potential for abuse. Consequently, the FDA is now subjecting psychedelic therapies to more rigorous review, particularly regarding blinding methodologies and comprehensive safety data. Challenges inherent in blinding trials with psychoactive substances, where participants and therapists often discern the active drug, remain a significant hurdle, as does the FDA's demand for more extensive long-term safety and efficacy data. Several critical dates before January 1, 2027, will shape market probability. Q1 2026 is crucial for Compass Pathways, with the expected release of 26-week results from COMP005 and full data from Part A of COMP005 and COMP006. This is followed by a highly anticipated NDA filing for COMP360 by Q3 2026. Additionally, MindMed's LSD program is set to release Phase 3 data in late 2026. These upcoming data readouts and regulatory submissions are pivotal, with industry predictions indicating a strong likelihood of FDA approvals for both Definium's DT120 and Compass Pathways' COMP360 by 2027, provided these catalysts unfold positively.